BRPI0616707A2 - inibidores de renina, seus processos de fabricação e seu uso - Google Patents

inibidores de renina, seus processos de fabricação e seu uso Download PDF

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Publication number: BRPI0616707A2
Authority: BR; Brazil
Prior art keywords: formula; compound; alkyl; salt; methoxy
Prior art date: 2005-09-28

Application number

BRPI0616707-1A

Other languages

English (en)

Portuguese (pt)

Inventor

Stuart John Mickel

Wolfgang Marterer

Original Assignee

Novartis Ag

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

2005-09-28

Filing date

2006-09-26

Publication date

2011-06-28

Family has litigation

First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=35394904&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=BRPI0616707(A2) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.

2006-09-26 Application filed by Novartis Ag filed Critical Novartis Ag

2011-06-28 Publication of BRPI0616707A2 publication Critical patent/BRPI0616707A2/pt

Links

238000004519 manufacturing process Methods 0.000 title claims abstract description 60
239000002461 renin inhibitor Substances 0.000 title claims abstract description 42
229940086526 renin-inhibitors Drugs 0.000 title claims abstract description 42
150000001875 compounds Chemical class 0.000 claims abstract description 342
150000003839 salts Chemical class 0.000 claims abstract description 150
238000000034 method Methods 0.000 claims abstract description 102
230000008569 process Effects 0.000 claims abstract description 64
-1 glycine compound Chemical class 0.000 claims description 139
238000006243 chemical reaction Methods 0.000 claims description 110
125000000217 alkyl group Chemical group 0.000 claims description 52
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 48
239000002253 acid Substances 0.000 claims description 48
125000006239 protecting group Chemical group 0.000 claims description 43
239000001257 hydrogen Substances 0.000 claims description 29
229910052739 hydrogen Inorganic materials 0.000 claims description 29
150000002148 esters Chemical class 0.000 claims description 27
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 24
125000004183 alkoxy alkyl group Chemical group 0.000 claims description 21
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 18
230000007062 hydrolysis Effects 0.000 claims description 16
238000006460 hydrolysis reaction Methods 0.000 claims description 16
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 15
125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 14
238000005984 hydrogenation reaction Methods 0.000 claims description 14
125000006701 (C1-C7) alkyl group Chemical group 0.000 claims description 11
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Natural products NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 11
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 11
125000003710 aryl alkyl group Chemical group 0.000 claims description 9
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 9
150000001336 alkenes Chemical class 0.000 claims description 8
125000003545 alkoxy group Chemical group 0.000 claims description 8
JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 claims description 8
238000006352 cycloaddition reaction Methods 0.000 claims description 6
150000002466 imines Chemical group 0.000 claims description 5
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 4
239000004471 Glycine Substances 0.000 claims description 3
238000002360 preparation method Methods 0.000 claims description 3
125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims description 2
125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 4
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 1
101100412446 Caenorhabditis elegans rer-1 gene Proteins 0.000 claims 1
DZJXKISLUDYJSV-UHFFFAOYSA-N [N].C1CCNC1 Chemical compound [N].C1CCNC1 DZJXKISLUDYJSV-UHFFFAOYSA-N 0.000 claims 1
125000004744 butyloxycarbonyl group Chemical group 0.000 claims 1
125000004185 ester group Chemical group 0.000 claims 1
230000015572 biosynthetic process Effects 0.000 abstract description 79
238000003786 synthesis reaction Methods 0.000 abstract description 77
UXOWGYHJODZGMF-QORCZRPOSA-N Aliskiren Chemical compound COCCCOC1=CC(C[C@@H](C[C@H](N)[C@@H](O)C[C@@H](C(C)C)C(=O)NCC(C)(C)C(N)=O)C(C)C)=CC=C1OC UXOWGYHJODZGMF-QORCZRPOSA-N 0.000 abstract description 35
229960004601 aliskiren Drugs 0.000 abstract description 35
239000000543 intermediate Substances 0.000 abstract description 25
239000003112 inhibitor Substances 0.000 abstract description 5
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 63
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 62
239000002904 solvent Substances 0.000 description 62
239000000243 solution Substances 0.000 description 58
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 57
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 54
238000005160 1H NMR spectroscopy Methods 0.000 description 52
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 51
239000000203 mixture Substances 0.000 description 47
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 37
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 36
239000002585 base Substances 0.000 description 32
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 30
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 25
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 25
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 24
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 24
239000003921 oil Substances 0.000 description 24
239000012074 organic phase Substances 0.000 description 24
239000003054 catalyst Substances 0.000 description 22
IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 20
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 19
125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 19
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical group C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 18
150000001299 aldehydes Chemical class 0.000 description 18
125000002887 hydroxy group Chemical group [H]O* 0.000 description 18
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 18
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 18
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 17
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 17
229910052751 metal Inorganic materials 0.000 description 17
239000002184 metal Substances 0.000 description 17
230000009467 reduction Effects 0.000 description 17
238000006722 reduction reaction Methods 0.000 description 17
239000007787 solid Substances 0.000 description 17
239000003153 chemical reaction reagent Substances 0.000 description 16
239000000725 suspension Substances 0.000 description 16
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 14
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 13
BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 13
RTZKZFJDLAIYFH-UHFFFAOYSA-N diethyl ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 13
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 12
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 12
229910052757 nitrogen Inorganic materials 0.000 description 12
238000010992 reflux Methods 0.000 description 12
230000003647 oxidation Effects 0.000 description 11
238000007254 oxidation reaction Methods 0.000 description 11
230000001590 oxidative effect Effects 0.000 description 11
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
239000011701 zinc Substances 0.000 description 10
239000013543 active substance Substances 0.000 description 9
239000006227 byproduct Substances 0.000 description 9
238000001914 filtration Methods 0.000 description 9
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 9
229910000069 nitrogen hydride Inorganic materials 0.000 description 9
229910052763 palladium Inorganic materials 0.000 description 9
BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 9
239000007858 starting material Substances 0.000 description 9
125000001424 substituent group Chemical group 0.000 description 9
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 8
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 8
229960000583 acetic acid Drugs 0.000 description 8
239000000460 chlorine Substances 0.000 description 8
238000010511 deprotection reaction Methods 0.000 description 8
229960001760 dimethyl sulfoxide Drugs 0.000 description 8
238000011065 in-situ storage Methods 0.000 description 8
150000007530 organic bases Chemical class 0.000 description 8
238000007142 ring opening reaction Methods 0.000 description 8
GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 8
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 7
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 7
WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 7
239000003638 chemical reducing agent Substances 0.000 description 7
229910052801 chlorine Inorganic materials 0.000 description 7
239000010949 copper Substances 0.000 description 7
229960002449 glycine Drugs 0.000 description 7
150000002431 hydrogen Chemical group 0.000 description 7
150000007529 inorganic bases Chemical class 0.000 description 7
125000001624 naphthyl group Chemical group 0.000 description 7
239000000047 product Substances 0.000 description 7
CQLFBEKRDQMJLZ-UHFFFAOYSA-M silver acetate Chemical compound [Ag+].CC([O-])=O CQLFBEKRDQMJLZ-UHFFFAOYSA-M 0.000 description 7
GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 6
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 6
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 6
XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 6
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
230000002378 acidificating effect Effects 0.000 description 6
125000002252 acyl group Chemical group 0.000 description 6
150000001408 amides Chemical class 0.000 description 6
229910052794 bromium Inorganic materials 0.000 description 6
229910052799 carbon Inorganic materials 0.000 description 6
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 6
229910052744 lithium Inorganic materials 0.000 description 6
239000011777 magnesium Substances 0.000 description 6
239000007800 oxidant agent Substances 0.000 description 6
108090000765 processed proteins & peptides Proteins 0.000 description 6
230000035484 reaction time Effects 0.000 description 6
239000000741 silica gel Substances 0.000 description 6
229910002027 silica gel Inorganic materials 0.000 description 6
235000017557 sodium bicarbonate Nutrition 0.000 description 6
229910000030 sodium bicarbonate Inorganic materials 0.000 description 6
229910052725 zinc Inorganic materials 0.000 description 6
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 5
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 5
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 5
150000001298 alcohols Chemical class 0.000 description 5
235000001014 amino acid Nutrition 0.000 description 5
239000007864 aqueous solution Substances 0.000 description 5
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 5
150000004820 halides Chemical class 0.000 description 5
150000008282 halocarbons Chemical class 0.000 description 5
229910052736 halogen Inorganic materials 0.000 description 5
150000002367 halogens Chemical class 0.000 description 5
239000011734 sodium Substances 0.000 description 5
RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 5
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
102000005862 Angiotensin II Human genes 0.000 description 4
101800000733 Angiotensin-2 Proteins 0.000 description 4
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 4
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 4
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 4
CZGUSIXMZVURDU-JZXHSEFVSA-N Ile(5)-angiotensin II Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC=1C=CC=CC=1)C([O-])=O)NC(=O)[C@@H](NC(=O)[C@H](CCCNC(N)=[NH2+])NC(=O)[C@@H]([NH3+])CC([O-])=O)C(C)C)C1=CC=C(O)C=C1 CZGUSIXMZVURDU-JZXHSEFVSA-N 0.000 description 4
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 4
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 4
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 4
SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 4
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
LOUPRKONTZGTKE-WZBLMQSHSA-N Quinine Chemical compound C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@@H]2[C@H](O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-WZBLMQSHSA-N 0.000 description 4
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
150000001413 amino acids Chemical class 0.000 description 4
235000019270 ammonium chloride Nutrition 0.000 description 4
229950006323 angiotensin ii Drugs 0.000 description 4
150000008064 anhydrides Chemical class 0.000 description 4
238000013459 approach Methods 0.000 description 4
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 4
FUSUHKVFWTUUBE-UHFFFAOYSA-N buten-2-one Chemical compound CC(=O)C=C FUSUHKVFWTUUBE-UHFFFAOYSA-N 0.000 description 4
125000004432 carbon atom Chemical group C* 0.000 description 4
238000004587 chromatography analysis Methods 0.000 description 4
229910052802 copper Inorganic materials 0.000 description 4
229960004132 diethyl ether Drugs 0.000 description 4
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
238000001035 drying Methods 0.000 description 4
229940052303 ethers for general anesthesia Drugs 0.000 description 4
239000011737 fluorine Substances 0.000 description 4
229910052731 fluorine Inorganic materials 0.000 description 4
238000005755 formation reaction Methods 0.000 description 4
235000013905 glycine and its sodium salt Nutrition 0.000 description 4
125000005843 halogen group Chemical group 0.000 description 4
239000002638 heterogeneous catalyst Substances 0.000 description 4
229930195733 hydrocarbon Natural products 0.000 description 4
150000002430 hydrocarbons Chemical class 0.000 description 4
238000002955 isolation Methods 0.000 description 4
ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 4
229910052749 magnesium Inorganic materials 0.000 description 4
NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 4
150000007522 mineralic acids Chemical class 0.000 description 4
150000007524 organic acids Chemical class 0.000 description 4
239000012044 organic layer Substances 0.000 description 4
UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 4
229910000073 phosphorus hydride Inorganic materials 0.000 description 4
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
102000004196 processed proteins & peptides Human genes 0.000 description 4
UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical compound OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 description 4
150000003235 pyrrolidines Chemical class 0.000 description 4
238000010898 silica gel chromatography Methods 0.000 description 4
229910052708 sodium Inorganic materials 0.000 description 4
WBHQBSYUUJJSRZ-UHFFFAOYSA-M sodium bisulfate Chemical compound [Na+].OS([O-])(=O)=O WBHQBSYUUJJSRZ-UHFFFAOYSA-M 0.000 description 4
229910000342 sodium bisulfate Inorganic materials 0.000 description 4
UFDULEKOJAEIRI-UHFFFAOYSA-N (2-acetyloxy-3-iodophenyl) acetate Chemical compound CC(=O)OC1=CC=CC(I)=C1OC(C)=O UFDULEKOJAEIRI-UHFFFAOYSA-N 0.000 description 3
FPIRBHDGWMWJEP-UHFFFAOYSA-N 1-hydroxy-7-azabenzotriazole Chemical compound C1=CN=C2N(O)N=NC2=C1 FPIRBHDGWMWJEP-UHFFFAOYSA-N 0.000 description 3
YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 description 3
QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 3
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125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 1
UCUUFSAXZMGPGH-UHFFFAOYSA-N penta-1,4-dien-3-one Chemical compound C=CC(=O)C=C UCUUFSAXZMGPGH-UHFFFAOYSA-N 0.000 description 1
125000000538 pentafluorophenyl group Chemical group FC1=C(F)C(F)=C(*)C(F)=C1F 0.000 description 1
239000000813 peptide hormone Substances 0.000 description 1
VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical class OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 1
239000012071 phase Substances 0.000 description 1
125000005561 phenanthryl group Chemical group 0.000 description 1
125000006678 phenoxycarbonyl group Chemical group 0.000 description 1
XYFCBTPGUUZFHI-UHFFFAOYSA-O phosphonium Chemical compound [PH4+] XYFCBTPGUUZFHI-UHFFFAOYSA-O 0.000 description 1
150000003017 phosphorus Chemical class 0.000 description 1
OXNIZHLAWKMVMX-UHFFFAOYSA-N picric acid Chemical class OC1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-N 0.000 description 1
239000002798 polar solvent Substances 0.000 description 1
125000003367 polycyclic group Chemical group 0.000 description 1
239000000843 powder Substances 0.000 description 1
150000003138 primary alcohols Chemical class 0.000 description 1
UBKCIXXGQRZHRO-UHFFFAOYSA-N propan-2-yl 2-aminoacetate;hydrochloride Chemical compound Cl.CC(C)OC(=O)CN UBKCIXXGQRZHRO-UHFFFAOYSA-N 0.000 description 1
235000019260 propionic acid Nutrition 0.000 description 1
HLIBNTOXKQCYMV-UHFFFAOYSA-N propylsulfamic acid Chemical compound CCCNS(O)(=O)=O HLIBNTOXKQCYMV-UHFFFAOYSA-N 0.000 description 1
229940070376 protein Drugs 0.000 description 1
UAGFTQCWTTYZKO-UHFFFAOYSA-N pyrrolidine-2-carboxylic acid;hydrochloride Chemical compound Cl.OC(=O)C1CCCN1 UAGFTQCWTTYZKO-UHFFFAOYSA-N 0.000 description 1
IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
150000003254 radicals Chemical class 0.000 description 1
230000036454 renin-angiotensin system Effects 0.000 description 1
238000011160 research Methods 0.000 description 1
150000003333 secondary alcohols Chemical class 0.000 description 1
229910052709 silver Inorganic materials 0.000 description 1
239000010944 silver (metal) Substances 0.000 description 1
229910001923 silver oxide Inorganic materials 0.000 description 1
ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 1
229910001415 sodium ion Inorganic materials 0.000 description 1
159000000000 sodium salts Chemical class 0.000 description 1
AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
235000019345 sodium thiosulphate Nutrition 0.000 description 1
239000012453 solvate Substances 0.000 description 1
241000894007 species Species 0.000 description 1
238000010561 standard procedure Methods 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
239000008107 starch Substances 0.000 description 1
239000000126 substance Substances 0.000 description 1
125000000547 substituted alkyl group Chemical group 0.000 description 1
125000003107 substituted aryl group Chemical group 0.000 description 1
238000006467 substitution reaction Methods 0.000 description 1
IIACRCGMVDHOTQ-UHFFFAOYSA-N sulfamic acid group Chemical class S(N)(O)(=O)=O IIACRCGMVDHOTQ-UHFFFAOYSA-N 0.000 description 1
125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 description 1
125000000542 sulfonic acid group Chemical group 0.000 description 1
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical group C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 description 1
125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
OSBSFAARYOCBHB-UHFFFAOYSA-N tetrapropylammonium Chemical compound CCC[N+](CCC)(CCC)CCC OSBSFAARYOCBHB-UHFFFAOYSA-N 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
125000003396 thiol group Chemical class [H]S* 0.000 description 1
239000011135 tin Substances 0.000 description 1
229910052718 tin Inorganic materials 0.000 description 1
125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
230000001131 transforming effect Effects 0.000 description 1
125000005208 trialkylammonium group Chemical group 0.000 description 1
ILWRPSCZWQJDMK-UHFFFAOYSA-N triethylazanium;chloride Chemical compound Cl.CCN(CC)CC ILWRPSCZWQJDMK-UHFFFAOYSA-N 0.000 description 1
125000005951 trifluoromethanesulfonyloxy group Chemical group 0.000 description 1
125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
230000025033 vasoconstriction Effects 0.000 description 1
238000005406 washing Methods 0.000 description 1
239000011787 zinc oxide Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C249/00—Preparation of compounds containing nitrogen atoms doubly-bound to a carbon skeleton
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C251/00—Compounds containing nitrogen atoms doubly-bound to a carbon skeleton
- C07C251/02—Compounds containing nitrogen atoms doubly-bound to a carbon skeleton containing imino groups
- C07C251/24—Compounds containing nitrogen atoms doubly-bound to a carbon skeleton containing imino groups having carbon atoms of imino groups bound to carbon atoms of six-membered aromatic rings
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/12—Preparation of carboxylic acid amides by reactions not involving the formation of carboxamide groups
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/08—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon radicals, substituted by hetero atoms, attached to ring carbon atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D207/16—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals

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Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Chemical Kinetics & Catalysis (AREA)
Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Animal Behavior & Ethology (AREA)
Bioinformatics & Cheminformatics (AREA)
Pharmacology & Pharmacy (AREA)
Engineering & Computer Science (AREA)
General Health & Medical Sciences (AREA)
Cardiology (AREA)
Heart & Thoracic Surgery (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Pyrrole Compounds (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Plural Heterocyclic Compounds (AREA)
Furan Compounds (AREA)

BRPI0616707-1A 2005-09-28 2006-09-26 inibidores de renina, seus processos de fabricação e seu uso BRPI0616707A2 (pt)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
GB0519764.5		2005-09-28
GBGB0519764.5A GB0519764D0 (en)	2005-09-28	2005-09-28	Organic compounds
PCT/EP2006/009323 WO2007039183A1 (en)	2005-09-28	2006-09-26	Sythesis of renin inhibitors involving a cycloaddition reaction

Publications (1)

Publication Number	Publication Date
BRPI0616707A2 true BRPI0616707A2 (pt)	2011-06-28

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BRPI0616707-1A BRPI0616707A2 (pt)	2005-09-28	2006-09-26	inibidores de renina, seus processos de fabricação e seu uso

Country Status (27)

Country	Link
US (2)	US7973175B2 (de)
EP (2)	EP1931629B1 (de)
JP (1)	JP2009509990A (de)
KR (1)	KR20080048042A (de)
CN (1)	CN101273012A (de)
AR (1)	AR057137A1 (de)
AT (1)	ATE492533T1 (de)
AU (1)	AU2006299097B2 (de)
BR (1)	BRPI0616707A2 (de)
CA (1)	CA2623495A1 (de)
DE (1)	DE602006019114D1 (de)
EC (1)	ECSP088319A (de)
ES (1)	ES2358536T3 (de)
GB (1)	GB0519764D0 (de)
GT (1)	GT200600427A (de)
IL (1)	IL189763A0 (de)
MA (1)	MA29852B1 (de)
MY (1)	MY143251A (de)
NO (1)	NO20082005L (de)
NZ (1)	NZ566429A (de)
PE (1)	PE20070488A1 (de)
PL (1)	PL1931629T3 (de)
PT (1)	PT1931629E (de)
RU (1)	RU2423348C2 (de)
TN (1)	TNSN08142A1 (de)
TW (1)	TW200730480A (de)
WO (1)	WO2007039183A1 (de)

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EP2062874B1 (de)	2007-11-20	2014-12-17	KRKA, tovarna zdravil, d.d., Novo mesto	Verfahren und Zwischenprodukte für die Herstellung von Aliskiren
EP2189442B1 (de)	2008-11-20	2014-10-01	Krka Tovarna Zdravil, D.D., Novo Mesto	Verfahren und Zwischenprodukte für die Herstellung von Aliskiren
US8203005B2 (en)	2009-10-29	2012-06-19	Carbo Design Llc	Manufacturing process for enantiomerically pure 8-aryloctanoic acids as Aliskiren
CN101774986B (zh) *	2010-01-06	2012-03-28	浙江天宇药业股份有限公司	一种制备阿利克伦及其中间体的方法
CN101863796B (zh) *	2010-05-12	2011-08-24	海南美兰史克制药有限公司	一种阿利克仑化合物及其制法
EP2551260A1 (de)	2011-07-28	2013-01-30	Chemo Ibérica, S.A.	Chemisches Verfahren zum Öffnen von Ringverbindungen
US8703976B2 (en)	2011-10-02	2014-04-22	Milan Soukup	Manufacturing process for 8-aryloctanoic acids such as Aliskiren

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DE3421295A1 (de)	1984-06-08	1985-12-12	Basf Ag, 6700 Ludwigshafen	Neue pyrrolidincarbonsaeurederivative, verfahren zu ihrer herstellung
MY119161A (en)	1994-04-18	2005-04-30	Novartis Ag	Delta-amino-gamma-hydroxy-omega-aryl-alkanoic acid amides with enzyme especially renin inhibiting activities
KR100690471B1 (ko)	2000-07-05	2007-03-09	스페델 파르마 아게	치환된 옥타노일 아미드의 제조방법
DE10116816A1 (de) *	2001-04-04	2002-10-17	Basf Ag	Verfahren zur Herstellung von N-Benzylaminen
GB0419361D0 (en)	2004-08-31	2004-10-06	Novartis Ag	Organic compounds

2005
- 2005-09-28 GB GBGB0519764.5A patent/GB0519764D0/en not_active Ceased
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- 2006-09-26 DE DE602006019114T patent/DE602006019114D1/de active Active
- 2006-09-26 JP JP2008532650A patent/JP2009509990A/ja active Pending
- 2006-09-26 CA CA002623495A patent/CA2623495A1/en not_active Abandoned
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- 2006-09-26 BR BRPI0616707-1A patent/BRPI0616707A2/pt not_active IP Right Cessation
- 2006-09-26 RU RU2008116317/04A patent/RU2423348C2/ru not_active IP Right Cessation
- 2006-09-26 AR ARP060104197A patent/AR057137A1/es not_active Application Discontinuation
- 2006-09-26 PL PL06805861T patent/PL1931629T3/pl unknown
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- 2006-09-26 PE PE2006001166A patent/PE20070488A1/es not_active Application Discontinuation
- 2006-09-26 EP EP06805861A patent/EP1931629B1/de not_active Not-in-force
- 2006-09-26 KR KR1020087007396A patent/KR20080048042A/ko not_active Ceased
- 2006-09-26 WO PCT/EP2006/009323 patent/WO2007039183A1/en not_active Ceased
- 2006-09-26 CN CNA2006800353469A patent/CN101273012A/zh active Pending
- 2006-09-26 US US12/067,055 patent/US7973175B2/en not_active Expired - Fee Related
- 2006-09-26 AT AT06805861T patent/ATE492533T1/de active
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- 2006-09-26 AU AU2006299097A patent/AU2006299097B2/en not_active Ceased
- 2006-09-26 EP EP10178025A patent/EP2287153A1/de not_active Withdrawn
- 2006-09-27 TW TW095135800A patent/TW200730480A/zh unknown
2008
- 2008-02-25 IL IL189763A patent/IL189763A0/en unknown
- 2008-03-27 EC EC2008008319A patent/ECSP088319A/es unknown
- 2008-03-27 TN TNP2008000142A patent/TNSN08142A1/en unknown
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- 2008-04-28 NO NO20082005A patent/NO20082005L/no not_active Application Discontinuation
2011
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Also Published As

Publication number	Publication date
WO2007039183A1 (en)	2007-04-12
ES2358536T3 (es)	2011-05-11
ATE492533T1 (de)	2011-01-15
PE20070488A1 (es)	2007-06-13
AU2006299097A1 (en)	2007-04-12
US20080255369A1 (en)	2008-10-16
IL189763A0 (en)	2008-08-07
US7973175B2 (en)	2011-07-05
ECSP088319A (es)	2008-04-28
AR057137A1 (es)	2007-11-21
PL1931629T3 (pl)	2011-05-31
CA2623495A1 (en)	2007-04-12
KR20080048042A (ko)	2008-05-30
DE602006019114D1 (de)	2011-02-03
NZ566429A (en)	2010-10-29
EP1931629A1 (de)	2008-06-18
CN101273012A (zh)	2008-09-24
JP2009509990A (ja)	2009-03-12
GB0519764D0 (en)	2005-11-09
NO20082005L (no)	2008-06-24
MY143251A (en)	2011-04-15
EP2287153A1 (de)	2011-02-23
PT1931629E (pt)	2011-03-09
EP1931629B1 (de)	2010-12-22
US20110230665A1 (en)	2011-09-22
TNSN08142A1 (en)	2009-07-14
MA29852B1 (fr)	2008-10-03
RU2423348C2 (ru)	2011-07-10
AU2006299097B2 (en)	2010-11-04
TW200730480A (en)	2007-08-16
GT200600427A (es)	2007-04-30
RU2008116317A (ru)	2009-11-10

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2016-03-29	B08K	Patent lapsed as no evidence of payment of the annual fee has been furnished to inpi [chapter 8.11 patent gazette]	Free format text: EM VIRTUDE DO ARQUIVAMENTO PUBLICADO NA RPI 2343 DE 01-12-2015 E CONSIDERANDO AUSENCIA DE MANIFESTACAO DENTRO DOS PRAZOS LEGAIS, INFORMO QUE CABE SER MANTIDO O ARQUIVAMENTO DO PEDIDO DE PATENTE, CONFORME O DISPOSTO NO ARTIGO 12, DA RESOLUCAO 113/2013.

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